Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo.
Platelet-derived growth factor (PDGF) is a potent mitogen for mesenchymal cells. Induction of the PDGF receptor-alpha (PDGF-R alpha) in vitro enhances PDGF-induced mitogenesis and chemotaxis. Thus we investigated whether the PDGF-R alpha is induced in vivo during pulmonary fibrogenesis using a vanadium pentoxide (V2O5) model of lung injury. PDGF-R alpha mRNA expression was induced 24 h postinstillation. PDGF-R beta mRNA was constitutively expressed and did not increase. Western blotting showed upregulation of PDGF-R alpha protein by 48 h, and immunohistochemical analysis localized PDGF-R alpha primarily in mesenchymal cells residing within fibrotic lesions. Upregulation of PDGF-R alpha in vivo preceded mesenchymal cell hyperplasia (3-7 days) and collagen deposition by day 15. Supernatants from alveolar macrophages treated with V2O5 in vitro released upregulatory activity for PDGF-R alpha on cultured lung myofibroblasts, and this activity was blocked by the interleukin-1-receptor antagonist. These data suggest that interleukin-1 beta-mediated induction of PDGF-R alpha in vivo is important to lung myofibroblast hyperplasia during fibrogenesis.
Bonner
J C
JC
Laboratory of Pulmonary Pathobiology, Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Lindroos
P M
PM
Rice
A B
AB
Moomaw
C R
CR
Morgan
D L
DL
D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D017968:Vanadium Compounds / Q000633:toxicity
D012333:RNA, Messenger; D017968:Vanadium Compounds; C066075:vanadium pentoxide; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor